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Expression profile of prostate cancer

a prostate cancer and expression profile technology, applied in the field of cancer diagnostics, can solve the problems of prostate specific antigen failure risk, prognosis comprises a risk of prostate cancer, and prognosis comprises a risk of prostate cancer, and achieve the effect of inhibiting ezh2 expression and reducing cell proliferation

Inactive Publication Date: 2007-06-12
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0036]The present invention additionally provides a method of inhibiting the growth of cells, comprising providing a cell that expresses EZH2; and a reagent for inhibiting EZH2 expression in the cell; and contacting the cell with the reagent under conditions such that the expression of EZH2 in the cell is inhibited. In some embodiments, the reagent is an antisense oligonucleotide. In other embodiments, the reagent is a RNA duplex. In some embodiments, the reagent is a drug. In some embodiments, the cell is a prostate cancer cell. In some embodiments, the cell is in vitro; while in other embodiments, the cell is in vivo. In some embodiments, the contacting further results in a decrease in proliferation of the cell.

Problems solved by technology

In some embodiments, the prognosis comprises a risk of developing prostate specific antigen failure.
In other embodiments, the prognosis comprises a risk of developing prostate cancer.
In some embodiments, the prognosis comprises a risk of developing prostate specific antigen failure.
In other embodiments, the prognosis comprises a risk of developing prostate cancer.

Method used

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  • Expression profile of prostate cancer
  • Expression profile of prostate cancer
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Examples

Experimental program
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example 1

Preparation of Total RNA and Reference Pools

[0319]The prostate surgical specimens were obtained from The University of Michigan Specialized Research Program in Prostate Cancer (S.P.O.R.E.) Tumor Bank with Institutional Review Board approval. Tumors samples were derived from patients with clinically localized and advanced hormone refractory prostate cancer. Table 1 shows the samples used in the present studies. All patients were operated on between 1993 and 1998 for clinically localized prostate cancer as determined by preoperative PSA, digital-rectal examination, and prostate needle biopsy. In addition, a subset of patients received bone and CAT scans to evaluate the possibility of metastatic spread. All patients received radical prostatectomy as a monotherapy (i.e., no hormonal or radiation therapy). The advanced prostate tumors were collected from a series of 12 rapid autopsies performed at the University of Michigan on men who died of hormone refractory prostate cancer. In brief,...

example 2

Microarray Analysis

[0322]This example describes the use of microarray analysis to identify genes that demonstrate an altered level of expression in cancerous or benign prostate tissues.

A. Experimental Methods

[0323]Microarray analysis of gene expression was conducted essentially as described by the Brown and Derisi Labs (available at the Internet site www.microarrays.org). The sequence-verified cDNA clones on the human cDNA microarray are available from the web site of Research Genetics. Based on the latest Unigene build, the 10K human cDNA microarray used covers approximately 5520 known, named genes and 4464 ESTs. All chips have various control elements that include human, rat, and yeast genomic DNAs, SSC, yeast genes and “housekeeping genes,” among others. In addition, 500 cancer- and apoptosis-related cDNAs from Research Genetics were used to serve as independent controls for clone tracking and function as duplicates for quality control. Three metastatic prostate cancer cell lines...

example 3

Northern Blot Analysis

[0347]Thirty micrograms of total RNA was resolved by denaturing formaldehyde agarose gel and transferred onto Hybond membrane (Amersham) by a capillary transfer set up. Hybridizations were performed by the method described by Church and Gilbert, 1984. Signal was visualized and quantitated by phosphorimager. For relative fold estimation, the ratio between the signals obtained from hepsin and GAPDH probes was calculated.

[0348]Selected genes identified by microarray analysis were corroborated by Northern analysis. For example, hevin, 4 1 / 2 LIM domain protein and gelsolin were shown to be 3.2-, 3.2- and 1.9-fold down-regulated, respectively by microarray and 8.8-, 4.5-, and 3.5-fold down-regulated by Northern analysis. Similarly, hepsin was 4.3-fold up-regulated by microarray and 11.3-fold up-regulated by Northern analysis (FIG. 3a). As bepsin is a cell-surface serine protease with transcript expression precisely restricted to localized and metastatic PCA, its expr...

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Abstract

The present invention relates to compositions and methods for cancer diagnostics, including but not limited to, cancer markers. In particular, the present invention provides gene expression profiles associated with prostate cancers. Genes identified as cancer markers using the methods of the present invention find use in the diagnosis and characterization of prostate cancer. In addition, the genes provide targets for cancer drug screens and therapeutic applications.

Description

[0001]This application claims priority to U.S. Provisional Application Ser. No. 60 / 309,581 filed Aug. 2, 2001 and U.S. Provisional Application Ser. No. 60 / 334,468 filed Nov. 15, 2001.[0002]This invention was made with government support under Grant No. 5 P50 CA69568 awarded by the National Institutes of Health. The Government has certain rights in the invention.[0003]Filed herewith as Tables 3, 4, 5, 6, and 7, and expressly incorporated by reference is an appendix contained on one compact disc, submitted in two identical sets labeled “Copy 1” and “Copy 2,” for a total of two compact discs. Each compact disc was prepared in IBM-PC machine format and is compatible with the MS-Windows operating system. The set of two compact discs contains the following 5 files, in ASCII format:[0004]Disc 1File NameCreation DateSize (bytes)table3.txtAug. 01, 20021,964,212table4.txtAug. 01, 20021,498,092table5.txtAug. 01, 20023,374,515table6.txtAug. 01, 200282,030table7.txtAug. 01, 200218,882FIELD OF TH...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): G01N33/53C07K14/435C12Q1/68C12N15/09C12Q1/02G01N33/15G01N33/50G01N33/566G01N33/574
CPCC12Q1/6886G01N33/57434C12Q2600/158Y10S436/813Y10S436/811
Inventor CHINNAIYAN, ARUL M.RUBIN, MARK A.SREEKUMAR, ARUN
Owner RGT UNIV OF MICHIGAN
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